Project Summary/Abstract The goal of the proposed project is to advance the research projects at The Jackson Laboratory (JAX) and throughout the research community using monoclonal antibodies in their research by acquiring a label-free protein screening instrument, the Octet HTX protein screener. JAX researchers increasingly rely on antibodies in their research programs, which are focused on understanding a broad range of human diseases. In response to the difficulty in identifying high-quality, reliable monoclonal antibodies for specific research applications, in 2015 JAX established the Monoclonal Antibody Service (MAS) on the Bar Harbor campus. This Service has successfully provided subsidized yet quality-controlled antibodies to internal JAX researchers and external collaborators, and now our Service is open to researchers around the globe through JAX Mice & Clinical Research Services, the commercial wing of JAX. The MAS uses hybridoma technology and high- throughput screening strategies to provide reliable custom antibodies. JAX researchers are now increasingly focusing on the use of antibodies for difficult targets such as proteins expressed at low levels, post- translational modifications, bacteria, and allergens, and on the application of blocking/neutralizing antibodies, and binders against human proteins for diagnostic/clinical applications. However, the current approaches in the MAS lack the capacities to identify reliable high-affinity antibodies for these studies. Specifically, the current approaches lack the sensitivity, throughput capacity, and capacity for identifying epitope-specific antibodies to rapidly and conclusively identify the high-affinity antibodies JAX researchers need. In contrast, the Octet HTX from Fortbio can perform kinetic measurements of molecular interactions involving antibodies; epitope binning, to identify antibodies against distinct antigen subpopulations; and antibody quantitation and isotyping, all at high throughput. Access to this instrument for antibody discovery will be critically important for a broad range of research at JAX, including microbiome studies, with development of antibodies against selected bacteria; allergy studies, with development of antibodies against specific allergens; investigation of the metabolic pathways of T cells that regulate their function and anti-tumor efficacy; studies to develop new immunodeficient mouse models; and the study of genes involved in anxiety-related behaviors, neuromuscular disease, and type 2 diabetes. Further, this state-of-the-art instrument will meet our investigators? needs well into the future.